DK161669B - SYNERGISTIC PHARMACEUTICAL PREPARATION FOR THE TREATMENT OF DEPRESSIVE SYMPTOMS, PROCEDURE FOR ITS PREPARATION AND APPLICATION OF THE PREPARED MIXTURE FOR THE PREPARATION OF THE PREPARATION - Google Patents
SYNERGISTIC PHARMACEUTICAL PREPARATION FOR THE TREATMENT OF DEPRESSIVE SYMPTOMS, PROCEDURE FOR ITS PREPARATION AND APPLICATION OF THE PREPARED MIXTURE FOR THE PREPARATION OF THE PREPARATION Download PDFInfo
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Description
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Den foreliggende opfindelse angår et synergistisk farmaceutisk præparat til behandling af depressive symptomer, en fremgangsmåde til dets fremstilling og anvendelse af den fremstillede blanding til præparatets fremstilling.The present invention relates to a synergistic pharmaceutical composition for the treatment of depressive symptoms, a process for its preparation and the use of the prepared composition for the preparation of the composition.
5 Det er kendt, at symptomer på depression kan elimine res ved hjælp af en behandling med d-phenylalanin i 60-70% af tilfældene (jfr. Fischer m.fl., Arzneim, Forsch. 25, 132 (1975), Spatz m.fl., Biol. Psychiat. 10, 235-238 (1975)), medens d,l-phenylalanin ved indgivelse i en daglig dosis på 10 højst 200 mg er effektiv i 60% af tilfældene (jfr. Beckmann ml.fl., J. neural Transm. 41, 123-134 (1977)). Under behandlingen af patienter, som lider af Parkinsons syge, med infusion af l-phenylalanin er det blevet konstateret, at dysphori, som er et samtidigt forekommende fænomen ved Par-15 kinssons syge, nedsættes (jfr. Birkmayer, Wiener Zeitsch. fur Nervenheilkunde 13, 128-139 (1966)).5 It is known that symptoms of depression can be eliminated by treatment with d-phenylalanine in 60-70% of cases (cf. Fischer et al., Arzneim, Forsch. 25, 132 (1975), Spatz et al. et al., Biol., Psychiat. 10, 235-238 (1975)), while d, l-phenylalanine when administered at a daily dose of 10 maximum 200 mg is effective in 60% of cases (cf. Beckmann et al. , J. Neural Transm. 41, 123-134 (1977)). In the treatment of patients suffering from Parkinson's disease with infusion of l-phenylalanine, it has been found that dysphoria, which is a co-occurring phenomenon of Par-15 kinsson's disease, is reduced (cf. Birkmayer, Wiener Zeitsch. Fur Nervenheilkunde 13 , 128-139 (1966)).
Ved tidligere åbne kliniske prøver (jfr. Varga og Tringer, Acta med. Acad. Sci. Hung. 23^ 289-295 (1967)) er der opnået en væsentlig forbedring af de 20 kliniske billeder af depression ved indgivelse af (+)--deprenyl, dvs. N-(1-phenylisopropyl)-N-methyl-N-pro-pinylamin-hydrochlorid, i daglige doser på 50-100 mg.Previously open clinical trials (cf. Varga and Tringer, Acta Med. Acad. Sci. Hung. 23 ^ 289-295 (1967)) have significantly improved the 20 clinical pictures of depression by administration of (+) - -deprenyl, i.e. N- (1-phenylisopropyl) -N-methyl-N-propinylamine hydrochloride, in daily doses of 50-100 mg.
(-)-Deprenyl er en kraftig specifikt monoamin-oxydase B enzyminhiberende forbindelse, hvorimod (+)-25 -isomeren primært har amphetaminaktivitet og i det væsentlige er ansvarlig for racematets antidepressive virkning således som rapporteret i de tidligere publikationer.(-) - Deprenyl is a potent specific monoamine oxidase B enzyme-inhibiting compound, whereas the (+) - 25 isomer has primarily amphetamine activity and is essentially responsible for the antidepressant effect of the racemate as reported in previous publications.
(-)-Deprenyls antidepressive aktivitet er ble-30 vet undersøgt af mange forfattere, jfr. således Mann m.fl., Life Sci. 26, 877-882 (1980), J. Clin. Psycho-pharm. 2, 54-57 (1982), der har fundet antidepressiv aktivitet ved daglige doser på hhv. 15 mg og 20 mg.(-) - Deprenyl's antidepressant activity has been studied by many authors, cf. thus Mann et al., Life Sci. 26, 877-882 (1980), J. Clin. Psycho-pharm. 2, 54-57 (1982), who have found antidepressant activity at daily doses, respectively. 15 mg and 20 mg.
Mendlewicz m.fl. (jfr. J. neural. Transm. 43, 279-286 35 (1978), J. Affective Disorders 2, 137-146 (1980)) ind gav den samme forbindelse i en daglig dosis på 15 mg 2Mendlewicz et al. (cf. J. Neural. Transm. 43, 279-286 (1978), J. Affective Disorders 2, 137-146 (1980)) administered the same compound at a daily dose of 15 mg 2.
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i kombination med 3 x 300 mg 5-OH-tryptophan og 3 x 75 mg benzerazid og iagttog antidepressiv aktivitet ligesom Liebowitz m.fl. (jfr. Internatonal Jumex Conference, maj 5-8, 1982 Szombathely), der indgav (-)-deprenyl i 5 daglig dosis på 30 mg. Andre såsom Mendis m.fl. (jfr. Psychopharmacology 73, 87-90 (1981)) fandt ikke nogen bedre antidepressiv aktivitet end i tilfældet ved indgivelse af placebo, når forbindelsen blev indgivet i en daglig dosis på 20 mg.in combination with 3 x 300 mg of 5-OH-tryptophan and 3 x 75 mg of benzerazide and observed antidepressant activity like Liebowitz et al. (cf. Internatonal Jumex Conference, May 5-8, 1982 Szombathely), who administered (-) - deprenyl in 5 daily doses of 30 mg. Others such as Mendis et al. (cf. Psychopharmacology 73, 87-90 (1981)) found no better antidepressant activity than in the case of placebo administration when the compound was administered at a daily dose of 20 mg.
10 Det har nu vist sig, at en samtidig indgift af 1-phenylalanin (200-300 mg, men fortrinsvis 250 mg daglig) og af (-)-deprenyl anvendt indenfor det selektivt monoaminoxydase B-enzyminhiberende interval (fra 3-10 mg, men fortrinsvis fra 5-10 mg dagligt), og eventuelt 15 carbidopa, dvs. 3-(3,4-dihydroxyphenyl)-2-hydrazino-2--methylpropionsyre-monohydrat, i en daglig dosis på 20--30 mg eller benzerazid, dvs. N-(DL-seryl)-Ν'-(2,3,4--trihydroxybenzyl)-hydrazin, i en daglig dosis på 50--70 mg, kan der konstateres en væsentlig forøgelse af 20 den terapeutisk antidepressive aktivitet.It has now been found that concomitant administration of 1-phenylalanine (200-300 mg, but preferably 250 mg daily) and of (-) - deprenyl used within the selective monoamine oxidase B enzyme inhibitory range (from 3-10 mg, but preferably from 5-10 mg daily), and optionally 15 carbidopa, i.e. 3- (3,4-dihydroxyphenyl) -2-hydrazino-2-methylpropionic acid monohydrate, in a daily dose of 20--30 mg or benzerazide, i.e. N- (DL-seryl) -Ν '- (2,3,4 - trihydroxybenzyl) -hydrazine, at a daily dose of 50--70 mg, a significant increase in therapeutic antidepressant activity can be observed.
I overensstemmelse hermed er det her omhandlede, synergistiske farmaceutiske præparat til behandling af depressive symptomer ejendommeligt ved det i den kendetegnende del af krav 1 angivne.Accordingly, the present synergistic pharmaceutical composition for the treatment of depressive symptoms is peculiar to that of the characterizing portion of claim 1.
25 Tilsvarende er den her omhandlede fremgangsmåde til præparatets fremstilling ejendommelig ved det i den kendetegnende del af krav 5 angivne.Similarly, the method of the present invention for the preparation of the composition is peculiar to that of the characterizing part of claim 5.
Endelig angår opfindelsen anvendelsen af den ved fremgangsmåden fremstillede blanding af 1-phenylalanin og 30 (-)-deprenyl og eventuelt carbidopa eller benzerazid til fremstilling af et farmaceutisk præparat til behandling af depressive symptomer.Finally, the invention relates to the use of the mixture of 1-phenylalanine and 30 (-) - deprenyl and optionally carbidopa or benzerazide prepared by the process for the preparation of a pharmaceutical composition for the treatment of depressive symptoms.
Prøvemetoder.Test methods.
35 Ambulant behandling: Indenfor denne gruppe er 102 (44 mænd og 58 kvinder) patienter, som har lidt af 335 Outpatient treatment: Within this group are 102 (44 men and 58 women) patients who have suffered from 3
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unipolar kronisk depression i 3-15 år, blevet behandlet. Patienterne har været igennem mindst 5 depressive faser, og de tidligere anvendte antidepressive behandlinger har vist sig ineffektive til behandlingen af deres 5 sygdom. En kombination af 250 mg 1-phenylalanin og 5-10 mg (-)-deprenyl indgives oralt i en enkelt dosis hver morgen i 28-96 på hinanden følgende dage.unipolar chronic depression for 3-15 years, been treated. Patients have been through at least 5 depressive stages and the antidepressant treatments used previously have proved ineffective in treating their 5 illnesses. A combination of 250 mg of 1-phenylalanine and 5-10 mg of (-) - deprenyl is administered orally in a single dose every morning for 28-96 consecutive days.
Behandling af impatiens. I denne gruppe er 53 patienter (23 mænd og 30 kvinder), der har lidt af 10 alvorlig, unipolar, kronisk depression i 3-15 år, blevet behandlet. Patienterne har haft mindst 5 depressive faser, og de konventionelle antidepressive behandlinger, som de tidligere har modtaget, har vist sig ineffektive også i disse tilfælde. En kombination af 250 mg 1-phenyl-15 alanin og 10 mg (-)-deprenyl indgives intravenøst i en enkelt dosis hver morgen i 14-28 på hinanden følgende dage.Treatment of impatience. In this group, 53 patients (23 men and 30 women) who have suffered from 10 severe, unipolar, chronic depression for 3-15 years have been treated. Patients have had at least 5 depressive stages and the conventional antidepressant treatments they have previously received have proven ineffective in these cases as well. A combination of 250 mg of 1-phenyl-15 alanine and 10 mg of (-) - deprenyl is administered intravenously in a single dose every morning for 14-28 consecutive days.
Symptomerne på depression bedømmes kvantitativt på grundlag af en skala, der anvendes vidt udbredt in-20 denfor den internationale litteratur (jfr. Hamilton.The symptoms of depression are assessed quantitatively on the basis of a scale widely used in international literature (cf. Hamilton.
J. Neurol. Neurosurg. Psychiat. 2Z_, 56-61 (1960)), ved egen metode (jfr. Birkmayer m.fl. In. Masked Depression, Kielholz, P., udgivet på Verlaget H. Huber, Bern-Stutt-gart-Wien (1973)) og ved den kliniske metode, der har 25 vundet anerkendelse verden over.J. Neurol. Neurosurg. Psychiat. 2Z_, 56-61 (1960)), by own method (cf. Birkmayer et al. In Masked Depression, Kielholz, P., published at Verlaget H. Huber, Bern-Stutt-gart-Wien (1973)) and by the clinical method that has gained 25 recognition worldwide.
Forklaringen på den kraftige synergistiske aktivitet, som opnås ved den kombinerede behandling, er, at 1-phenylalanin er et forstadie, og (-)-deprenyl regulerer ved sin selektive monoaminoxydase B enzyminhibe-30 rende og optagelsesinhiberende aktivitet niveauet af cerebrale aminer på den måde, at de to virkninger får samme retning og i fællesskab underbygger og støtter hinanden.The explanation for the potent synergistic activity achieved by the combined treatment is that 1-phenylalanine is a precursor, and (-) - deprenyl, by its selective monoamine oxidase B enzyme inhibitory and uptake inhibitory activity, regulates the level of cerebral amines in this way. that the two effects have the same direction and jointly support and support each other.
Resultaterne er anført nedenfor i tabel I: 35The results are listed below in Table I: 35
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Tabel ITable I
Oral og intravenøs behandling af unipolar depression med 1-phenylalanin og (-)-deprenyl 5 _Oral and intravenous treatment of unipolar depression with 1-phenylalanine and (-) - deprenyl 5
Parameter for oral intravenøs ; behandling behandling depressionens varighed (år) 3-15 3-15 10 den kombinerede behandlings varighed 28-96 14-28 (dag) 14-28 1-phenylalanin-dosis (mg/dag) 250 250 15 (-)-deprenyl-dosis (mg/dag) 5-10 10Parameter for oral intravenous; treatment treatment duration of depression (years) 3-15 3-15 10 duration of combined treatment 28-96 14-28 (day) 14-28 1-phenylalanine dose (mg / day) 250 250 15 (-) - deprenyl dose (mg / day) 5-10 10
Resultat af behandling første tegn på bedring 20 (efter ..... uger) 1 til 3 1 til 3Result of treatment first signs of improvement 20 (after ..... weeks) 1 to 3 1 to 3
Bedring/helbredelse i % af totalt antal patienterImprovement / healing in% of total number of patients
Kureret 68,5 69,5 bedret 21,5 11,0 25 ingen bedring 6,0 12,0 ikke bedømt 4,0 7,5Cured 68.5 69.5 Improved 21.5 11.0 25 No Recovery 6.0 12.0 Not Rated 4.0 7.5
Bedømmelsen er gennemført ved den af Birkmayer ml.fl. beskrevne metode (jfr. ovenstående beskrivelse 30 af prøvemetoden). Patienternes gennemsnitsalder er 45 år (fra 18-80 år), og i begge grupperne udgør kvinder 60% af patienterne. De konventionelle antidepressive behandlinger har vist sig at slå fejl hos disse patienter.The assessment was conducted by Birkmayer et al. described method (cf. above description 30 of the test method). The average age of patients is 45 years (from 18 to 80 years), and in both groups, women make up 60% of patients. The conventional antidepressant treatments have been shown to fail in these patients.
I de synergistiske farmaceutiske midler ifølge 35 opfindelsen kan vægtforholdet mellem komponenterne varieres indenfor et bredt område, idet der anvendesIn the synergistic pharmaceutical agents of the invention, the weight ratio of the components can be varied within a wide range, using
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5 10-70 vægtdele, men fortrinsvis 25-50 vægtdele 1-phenyl-alanin pr. 1 vægtdel (-)-deprenyl. Benzerazidkomponen-ten anvendes i en mængde på 5-12 vægtdele, og carbidopa-et anvendes i en mængde på 2-6 vægtdele i forhold til 5 (-)-deprenyl.10 to 70 parts by weight, but preferably 25 to 50 parts by weight of 1-phenyl-alanine per unit weight. 1 part by weight (-) - deprenyl. The benzerazide component is used in an amount of 5-12 parts by weight and the carbidopa is used in an amount of 2-6 parts by weight relative to 5 (-) - deprenyl.
Ifølge opfindelsen kan det nye synergistiske middel overføres til konventionelle farmaceutiske præparatformer egnet til oral, parenteral, intravenøs indgift osv. Præparaterne fremstilles fortrinsvis i form 10 af tabletter, overtrukne tabletter, dragéer, kapsler eller injektionspræparater ved konventionel teknik som anvendt til præparationen af kendte farmaceutisk sammensætninger.According to the invention, the new synergistic agent can be transferred to conventional pharmaceutical formulations suitable for oral, parenteral, intravenous administration, etc. Preferably, the formulations are prepared in the form of tablets, coated tablets, dragees, capsules or injection preparations by conventional techniques as used in the preparation of known pharmaceutical compositions. .
Tabletterne eller injektionspræparaterne ifølge 15 opfindelsen indeholder fortrinsvis 250 mg 1-phenylala-nin og 5-10 mg (-)-deprenyl.The tablets or injections of the invention preferably contain 250 mg of 1-phenylalanine and 5-10 mg of (-) - deprenyl.
Til yderligere belysning af opfindelsen tjener følgende eksempler, hvori gennemgås visse repræsentative udførelsesformer under angivelse af nærmere detaljer.For further elucidation of the invention, the following examples serve to illustrate certain representative embodiments, with details being given.
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Eksempel 1Example 1
Dragéekerne 5,0 mg (-)-deprenyl-hydrochlorid 187,5 mg 1-phenylalanin 115,0 mg 25 lactose 15,5 mg stivelse 20,0 mg polyvidon 7,0 mg magneiumstearat 350,0 mg 30 overtræk "Luvisol" VA 64 13,0 mg talkum 10,0 mg titaniumdioxid 20,0 mg "Carbowax" 6000 7,0 mg 35 50,0 mgDragee core 5.0 mg (-) - deprenyl hydrochloride 187.5 mg 1-phenylalanine 115.0 mg 25 lactose 15.5 mg starch 20.0 mg polyvidone 7.0 mg magnesium stearate 350.0 mg 30 "Luvisol" VA coating 64 13.0 mg talc 10.0 mg titanium dioxide 20.0 mg Carbowax 6000 7.0 mg 50.0 mg
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Eksempel 2 Dragékerne (-)-deprenyl-hydrochlorid 5,0 mg 1-phenylalanin 50,0 mg 5 lactose 70,0 mg stivelse 9,5 mg polyvidon 12,5 mg magnesiumstearat 3,0 mg 150,0 mg 10 overtræk "Methocel" 60 Hg 15 cP 8,0 mg talkum 6,0 mg titaniumdioxid 12,0 mg "Carbowax" 6000 4,0 mg 15 30,0 mgExample 2 The dragon core (-) - deprenyl hydrochloride 5.0 mg 1-phenylalanine 50.0 mg 5 lactose 70.0 mg starch 9.5 mg polyvidone 12.5 mg magnesium stearate 3.0 mg 150.0 mg 10 coatings "Methocel 60 Hg 15 cP 8.0 mg talc 6.0 mg titanium dioxide 12.0 mg Carbowax 6000 4.0 mg 15 30.0 mg
Eksempel 3 Dragéekerne (-)-deprenyl 5,0 mg 20 1-phenylalanin 250,0 mg lactose 92,5 mg stivelse 19,0 mg polyvidon 25,5 mg magnesiumstearat 8,0 mg 25 400,0 mg overtræk "Luvisol" VA 64 6,5 mg "Methocel" 60 Hg 16 cP 6,5 mg 30 talkum 10,0 mg titaniumdioxid 22,0 mg "Carbowax" 6000 5,0 mg 50,0 mg 35Example 3 The dragees (-) - deprenyl 5.0 mg 20 1-phenylalanine 250.0 mg lactose 92.5 mg starch 19.0 mg polyvidone 25.5 mg magnesium stearate 8.0 mg 25 400.0 mg coating "Luvisol" VA 64 6.5 mg "Methocel" 60 Hg 16 cP 6.5 mg talc 10.0 mg titanium dioxide 22.0 mg Carbowax 6000 5.0 mg 50.0 mg
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præparationpreparation
Komponenterne ifølge ovenstående eksempler udvejes særskilt i de fornødne mængder til fremstilling af 10.000 dragéekerner. De to aktive bestanddele homo-s geniseres med den totale mængde lactose. Polyvidon opløses i 96%1 s ethanol under svag opvarmning. Homogenisa-tet af de aktive bestanddele og lactose æltes grundigt og homogeniseres med ovenstående granuleringsopløsning i et passende udstyr. Granulatet tørres ved en temperatur 10 på op til 35°C, indtil den fornødne fugtighedsgrad er opnået, og granuleres derpå igen. Til det opnåede granulat sættes stivelse, og der presses bikonvekse dragéekerner, som vejer hhv. 150, 350 og 400 mg. Overtrækssuspensionen fremstilles ved homogenisering af overtrækskomponenterne, 15 og bagefter opløses den opnåede blanding i isopropanol. Overtrækket påføres på dragéekernerne, som roteres, ved hjælp af et pneumatisk sprøjteanlæg. Overtrækket tørres med en luftstrøm på 35°C. Dragéerne poleres med en 1:1, blanding af isopropanol og vand indeholdende 10% Carbo-20 wax og emballeres på konventionel måde.The components of the above examples are weighed separately in the quantities required to produce 10,000 dragon cores. The two active ingredients are homo-sized with the total amount of lactose. Polyvidone is dissolved in 96% 1 s of ethanol under low heating. The homogenization of the active ingredients and lactose is thoroughly kneaded and homogenized with the above granulation solution in a suitable equipment. The granulate is dried at a temperature of 10 up to 35 ° C until the required humidity is obtained and then granulated again. Starch is added to the granules obtained, and biconvex dragon cores are pressed, which weigh respectively. 150, 350 and 400 mg. The coating suspension is prepared by homogenizing the coating components, and afterwards the resulting mixture is dissolved in isopropanol. The coating is applied to the dragon cores, which are rotated, by means of a pneumatic spray system. The coating is dried at an air flow of 35 ° C. The dragées are polished with a 1: 1 mixture of isopropanol and water containing 10% Carbo-20 wax and packaged in conventional manner.
Eksempel 4 (-)-deprenyl-hydrochlorid 5,0 mg 1-phenylalanin 250,0 mg 25 "Carbidopa" (ækvivalent med 25,0 mg 27,0 mg "Carbidopa"-anhydrat) lactose 25,5 mg stivelse 14,5 mg polyvidon 20,0 mg 30 magnesiumstearat 8,0 mg 350,0 mg 35Example 4 (-) - deprenyl hydrochloride 5.0 mg 1-phenylalanine 250.0 mg 25 "Carbidopa" (equivalent to 25.0 mg 27.0 mg "Carbidopa" anhydrate) lactose 25.5 mg starch 14.5 mg polyvidone 20.0 mg magnesium stearate 8.0 mg 350.0 mg 35
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Eksempel 5 (-)-deprenyl-hydrochlorid 5,0 mg 1-phenylalanin 250,0 mg benzerazid-hydrochlorid 71,25 mg 5 (svarende til 62,5 mg af benzerazid) lactose 23,75 mg stivelse 22,0 mg polyvidon 20,0 mg magnesiumstearat 8,0 mg 10 400,0 mgExample 5 (-) - deprenyl hydrochloride 5.0 mg 1-phenylalanine 250.0 mg benzerazide hydrochloride 71.25 mg 5 (corresponding to 62.5 mg of benzerazide) lactose 23.75 mg starch 22.0 mg polyvidone 20 , 0 mg magnesium stearate 8.0 mg 10 400.0 mg
Præparation af de ovenfor anførte kombinationer;Preparation of the above mentioned combinations;
Granulatet fremstilles ud fra komponenterne således som beskrevet i eksempel 1-3, og det fyldes der-15 på i kapsler af passende størrelse på en hensigtsmæssigt udstyr og emballeres på kendt måde.The granulate is prepared from the components as described in Examples 1-3, and it is then filled into capsules of appropriate size on a suitable equipment and packaged in known manner.
20 25 30 3520 25 30 35
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU434383 | 1983-12-20 | ||
| HU834343A HU193662B (en) | 1983-12-20 | 1983-12-20 | Process for producing synergetic pharmaceutical composition of antidepressive aktivity |
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| Publication Number | Publication Date |
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| DK612684D0 DK612684D0 (en) | 1984-12-19 |
| DK612684A DK612684A (en) | 1985-06-21 |
| DK161669B true DK161669B (en) | 1991-08-05 |
| DK161669C DK161669C (en) | 1992-01-27 |
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| DK612684A DK161669C (en) | 1983-12-20 | 1984-12-19 | SYNERGISTIC PHARMACEUTICAL PREPARATION FOR THE TREATMENT OF DEPRESSIVE SYMPTOMS, PROCEDURES FOR ITS PREPARATION AND APPLICATION OF THE PREPARED MIXTURE FOR THE PREPARATION OF THE PREPARATION |
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| US (1) | US4880833A (en) |
| EP (1) | EP0146363B1 (en) |
| JP (1) | JPH0713014B2 (en) |
| BG (1) | BG60400B2 (en) |
| DE (1) | DE3475164D1 (en) |
| DK (1) | DK161669C (en) |
| HK (1) | HK95091A (en) |
| HU (1) | HU193662B (en) |
| IE (1) | IE57759B1 (en) |
| IL (1) | IL73788A (en) |
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| ES2029805T3 (en) * | 1986-04-16 | 1992-10-01 | Asta Pharma Aktiengesellschaft | PROCEDURE FOR PREPARING A PRODUCT CONTAINING AMANTADINE AND SELEGILINE IN A SYNERGIC ASSOCIATION. |
| HU208484B (en) * | 1988-08-17 | 1993-11-29 | Chinoin Gyogyszer Es Vegyeszet | Process for producing pharmaceutical composition containing acid additional salt of selegilin as active component for treating schisofrenia |
| US5192808A (en) * | 1990-08-31 | 1993-03-09 | Deprenyl Animal Health, Inc. | Therapeutic effect of L-deprenyl in the management of pituitary-dependent hyperadrenocorticism (cushing's disease) |
| US5561163A (en) * | 1990-08-31 | 1996-10-01 | Deprenyl Animal Health, Inc. | Treating hearing loss with deprenyl |
| US5565495A (en) * | 1990-08-31 | 1996-10-15 | Deprenyl Animal Health, Inc. | Method for survival curve shifting in dogs |
| HUT63579A (en) * | 1991-12-20 | 1993-09-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing double-phase pharmaceutical compositions suitable for treating diseases occurring during neurodegenerative processes |
| US5817336A (en) * | 1993-04-02 | 1998-10-06 | Orion-Yhtyma Oy | Composition containing selegiline |
| SE9301112D0 (en) * | 1993-04-02 | 1993-04-02 | Orion-Yhtymae Oy | A NEW COMPOSITION |
| US5455276A (en) * | 1993-05-20 | 1995-10-03 | Sabelli; Hector C. | Method for treating depression |
| GB9426079D0 (en) * | 1994-12-23 | 1995-02-22 | Orion Yhtymae Oy | A gelatine capsule |
| US6316022B1 (en) | 1995-06-07 | 2001-11-13 | Noven Pharmaceuticals, Inc. | Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures |
| NZ309980A (en) * | 1995-06-07 | 2001-06-29 | Noven Pharma | Transdermal composition containing a blend of one or more polymers, one or more drugs that has a low molecular weight and is liquid at room temperature |
| KR100555336B1 (en) | 2001-12-18 | 2006-02-24 | 기와 가가쿠 고교 가부시키가이샤 | Ink for inkjet recording |
| GB0313630D0 (en) * | 2003-06-12 | 2003-07-16 | Wwk Trust The | Compositions for the enhanced treatment of depression |
| CN104788338A (en) * | 2014-10-17 | 2015-07-22 | 上海益生源药业有限公司 | Preparation method of benserazide hydrochloride |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1210873B (en) * | 1959-03-18 | 1966-02-17 | Hoffmann La Roche | Process for the preparation of haloalkylamines |
| US3362879A (en) * | 1965-01-11 | 1968-01-09 | Health Education Welfare Usa | Tyrosine tranquilizing compositions and methods of treatment |
| US4156017A (en) * | 1977-02-22 | 1979-05-22 | Schering Aktiengesellschaft | Pesticides |
| US4377595A (en) * | 1979-08-13 | 1983-03-22 | Massachusetts Institute Of Technology | Process for reducing depression |
| US4355044A (en) * | 1980-12-19 | 1982-10-19 | Bernardo Heller | D-Phenylalanine treatment |
| US4431670A (en) * | 1980-12-19 | 1984-02-14 | Bernardo Heller | D-Phenylalanine treatment |
-
1983
- 1983-12-20 HU HU834343A patent/HU193662B/en not_active IP Right Cessation
-
1984
- 1984-12-07 IE IE3149/84A patent/IE57759B1/en not_active IP Right Cessation
- 1984-12-11 IL IL73788A patent/IL73788A/en not_active IP Right Cessation
- 1984-12-14 DE DE8484308751T patent/DE3475164D1/en not_active Expired
- 1984-12-14 EP EP84308751A patent/EP0146363B1/en not_active Expired
- 1984-12-19 DK DK612684A patent/DK161669C/en not_active IP Right Cessation
- 1984-12-20 JP JP59269564A patent/JPH0713014B2/en not_active Expired - Lifetime
-
1986
- 1986-09-12 US US06/908,865 patent/US4880833A/en not_active Expired - Fee Related
-
1991
- 1991-11-28 HK HK950/91A patent/HK95091A/en not_active IP Right Cessation
-
1993
- 1993-12-02 BG BG98263A patent/BG60400B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE57759B1 (en) | 1993-03-24 |
| DK612684D0 (en) | 1984-12-19 |
| EP0146363B1 (en) | 1988-11-17 |
| DE3475164D1 (en) | 1988-12-22 |
| BG60400B2 (en) | 1995-02-28 |
| IL73788A0 (en) | 1985-03-31 |
| JPH0713014B2 (en) | 1995-02-15 |
| EP0146363A2 (en) | 1985-06-26 |
| DK612684A (en) | 1985-06-21 |
| US4880833A (en) | 1989-11-14 |
| IE843149L (en) | 1985-06-20 |
| DK161669C (en) | 1992-01-27 |
| HU193662B (en) | 1987-11-30 |
| HUT35517A (en) | 1985-07-29 |
| EP0146363A3 (en) | 1985-07-24 |
| JPS6110509A (en) | 1986-01-18 |
| HK95091A (en) | 1991-12-06 |
| IL73788A (en) | 1987-11-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |